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Toxicogenomics data sets on rat livers covering 118 compounds were subjected to inference of a gene set-level, not individual gene-level, network structure. Expression changing levels for 58 gene sets was used for network inference with a Gaussian graphical model algorithm. The established network contained reasonable relationships, such as ones between the blood glucose level and glycolysis-related...
Large-scale studies of mammalian genome transcription reveal that a large proportion of the genome is transcribed. It remains an open question whether the identified transcripts are functional. Here, we searched for computational evidence to support the functionality of 34,030 noncoding RNA (ncRNA) transcripts reported by the Fantom3 project. We show that compared to control sets, the Fantom ncRNA...
Small nucleolar RNAs (snoRNAs) represent one of the largest groups of functional non-protein coding RNAs currently known in eukaryotic cells. The processing of intron encoded snoRNAs has been well documented; however, the transcriptional regulation of snoRNA genes is still poorly understood, most likely due to the lack of characterization of snoRNA promoters. Here we used a computational approach...
Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. Results using whole genome Illumina microarrays show that ritonavir modulates a number of genes implicated in lipid metabolism, inflammation and atherosclerosis...
The activities of prokaryotes are pivotal in shaping the environment, and at the same time are greatly influenced by the environment. By using the genomic data and environmental descriptions of the complete prokaryotic genomes in NCBI's Microbial Genome Project Database and applying statistical methods, we have identified in a systematic manner those gene groups whose presence/frequency patterns are...
Polycomb group (PcG) proteins are important epigenetic regulators, yet the underlying targeting mechanism in mammals is still poorly understood. We have developed a computational approach to predict genome-wide PcG target genes in mouse embryonic stem cells. We use TF binding and motif information as predictors and apply the Bayesian Additive Regression Trees (BART) model for classification. Our model...
MicroRNAs (miRNAs) are endogenous non-protein-coding RNAs of approximately 22 nucleotides. Thousands of miRNA genes have been identified (computationally and/or experimentally) in a variety of organisms, which suggests that miRNA genes have been widely shared and distributed among species. Here, we used unique miRNA sequence patterns to scan the genome sequences of 56 bilaterian animal species for...
The brain responds to injury and infection by activating innate defense and tissue repair mechanisms. Working upon the hypothesis that the brain defense response involves common genes and pathways across diverse pathologies, we analysed global gene expression in brain from mouse models representing three major central nervous system disorders, cerebral stroke, multiple sclerosis and Alzheimer's disease...
The second codon of a transcript, besides encoding for an amino acid, is now known to also have multiple molecular functions and is involved in translation efficiency and protein turn-over and maturation processing. These multiple purposes therefore make the selection constraints on this codon's composition more complex. To examine the biological significance of various permutations of the second...
Transcription factors (TFs) are proteins that bind to specific promoter regions of their target genes and regulate gene transcription. Many of these factors have been found to influence flowering. Lycoris longituba exhibits a great deal of diversity in flower color and flower form, making it a suitable model for the study of floral development. We have identified 338 putative TFs from more than thirty...
The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy.To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor...
YPEL5 is a member of the YPEL gene family that is highly conserved in the eukaryotic species and apparently involved in a certain cell division-related function. In this study, we examined the functional and phylogenetic aspects of YPEL5 protein in more detail. During cell cycle, YPEL5 protein was detected at different subcellular localizations; at interphase, it was located in the nucleus and centrosome,...
Early studies suggested that most connexin genes share a relatively simple structure with a single intron of variable length interrupting the 5′ untranslated region (UTR). Here we report that zebrafish cx45.6 shows six isoforms of alternative 5′UTRs which are generated from multiple promoter usage and alternative pre-mRNA splicing. Interestingly, cx45.6 undergoes tandem alternative splicing, which...
While the methylation machinery of mammalian cells has been shown to be capable of both maintenance and de novo methylation at CpNpG sites, CpNpG methylation in the human genome has not been demonstrated. Here, we report the first observation of 5-methylcytosines in CpNpG triplets in the human genome. We identify the existence of CpNpG methylation in a number of genes which contain trinucleotide repeat...
Activated fibroblasts are the central effector cells of the progressive fibrotic process in idiopathic pulmonary fibrosis (IPF). Characterizing the genomic phenotype of isolated fibroblasts is essential to understanding IPF pathogenesis. Comparing the genomic phenotype of non-cultured pulmonary fibroblasts from advanced IPF patients' and normal lungs revealed novel genes, biological processes and...
Identification of different functional elements and their properties is a fundamental need in biomedical research and phylogenetic comparisons of a growing number of sequenced genomes form a solid basis for this task. Most available phylogenetic approaches are focused on searching for individual sequence alterations, responsible for the observed phenotype, or statistically evaluate observed mutations...
Non-protein-coding DNA comprises the majority of animal genomes but its functions are largely unknown. We identified over 17,000 different tetranucleotide pairs in the Drosophila melanogaster genome that are over-represented at distances up to 100nt in conserved non-exonic sequences. Those exhibiting the highest information content in surrounding nucleotides were classified into five groups: tRNAs,...
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